TGFB1 and neoplasm: Notably, TAMs significantly contribute to therapeutic resistance in PDAC through multiple pathways: (1) promoting dense stromal formation and IGF/IGF1R activation (43); (2) enhancing EMT-mediated drug evasion (44); (3) driving gemcitabine resistance via TGF-β1/Gfi-1 signaling, which can be attenuated by simvastatin (45); and (4) fostering immunotherapy resistance through CREB3L1-mediated TAM reprogramming within the tumor microenvironment (46).